Enhanced mobilization of the bone marrow-derived circulating progenitor cells by intracoronary freshly isolated bone marrow cells transplantation in patients with acute myocardial infarction

Abstract

Autologous bone marrow cell transplantation (BMCs-Tx) is a promising novel option for treatment of cardiovascular disease. We analysed in a randomized controlled study the influence of the intracoronary autologous freshly isolated BMCs-Tx on the mobilization of bone marrow-derived circulating progenitor cells (BM-CPCs) in patients with acute myocardial infarction (AMI). Sixty-two patients with AMI were randomized to either freshly isolated BMCs-Tx or to a control group without cell therapy. Peripheral blood (PB) concentrations of CD34/45(+) - and CD133/45(+)-circulating progenitor cells were measured by flow cytometry in 42 AMI patients with cell therapy as well as in 20 AMI patients without cell therapy as a control group on days 1, 3, 5, 7, 8 and 3, 6 as well as 12 months after AMI. Global ejection fraction (EF) and the size of infarct area were determined by left ventriculography. We observed in patients with freshly isolated BMCs-Tx at 3 and 12 months follow up a significant reduction of infarct size and increase of global EF as well as infarct wall movement velocity. The mobilization of CD34/45(+) and CD133/45(+) BM-CPCs significantly increased with a peak on day 7 as compared to baseline after AMI in both groups (CD34/45(+): P < 0.001, CD133/45(+): P < 0.001). Moreover, this significant mobilization of BM-CPCs existed 3, 6 and 12 months after cell therapy compared to day 1 after AMI. In control group, there were no significant differences of CD34/45(+) and CD133/45(+) BM-CPCs mobilization between day 1 and 3, 6 and 12 months after AMI. Intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system in patients with AMI may enhance and prolong the mobilization of CD34/45(+) and CD133/45(+) BM-CPCs in PB and this might increase the regenerative potency after AMI.

Fig 1

Enrolment and follow-up analysis of trial.

Fig 2

Global EF, infarct size and the wall movement velocity of the infarcted area were measured by left ventriculography baseline, 3 and 12 months after procedure in both groups. There were no significant baseline differences in global EF, infarct size and in infarct wall movement velocity between the two groups. Global EF and infarct wall movement velocity significantly increased 3 and 12 months after cell therapy compared to control group. Furthermore, there was a significant decrease of infarct size 3 and 12 months after cell transplantation compared to control group without cell therapy. Moreover, no significant changes were observed in the control group at follow-up.

Fig 3

NYHA classification and BNP levels in both groups. There were no significant differences of baseline NYHA classification and of BNP level between two groups; 3, 6 and 12 months after cell therapy there were a significant decrease of NYHA classification and of BNP level compared to control group without cell therapy. Moreover, no significant changes were observed in the control group at follow up.

Fig 4

The mobilization of CD34/45⁺ and CD133/45⁺ BM-CPCs increased significantly with a peak on day 7 after AMI. There was no significant difference between mobilization of both BM-CPCs on days 7, 8 as well as 3, 6 and 12 months after cell therapy. The significant increase of BM-CPCs after AMI exist also 3, 6 and 12 months after cell therapy as compared to day 1 after AMI.

Fig 5

The mobilization of CD34/45⁺ und CD133/45⁺ BM-CPCs increased significantly with a peak on day 7 after AMI, which significantly decreased on day 8 and 3, 6 and 12 months after AMI as compared to day 7. There was no significant difference between mobilization of both BM-CPCs on day 1 and on day 8 as well as 3, 6 and 12 months after AMI in patients without cell therapy.

Fig 6

There was significant increase of CD34/45⁺ and CD133/45⁺ BM-CPCs mobilization on days 7, 8 and 3, 6 and 12 months after AMI in BMCs-Tx group as compared control group without cell therapy, whereas there was no significant difference of BM-CPCs mobilization on days 1 and 7 after AMI between the BMCs-Tx group and control group without cell therapy.